Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), induce high morbidity and mortality rates, which challenge the present approaches for the treatment of ALI/ARDS. The clinically used photosensitizer verteporfin (VER) exhibits great potential in the treatment of acute lung injury and acute respiratory distress syndrome (ALI/ARDS) by regulating macrophage polarization and reducing inflammation. Nevertheless, its hydrophobic characteristics, nonspecificity, and constrained bioavailability hinder its therapeutic efficacy. In this work, we developed a type of VER-cored artificial exosome (EVM), which was produced by using mesoporous silica nanoparticles (MSNs) to load VER, followed by the exocytosis of internalized VER-MSNs from mouse bone marrow-derived mesenchymal stem cells (mBMSCs) without further modification. Both in vitro and in vivo assessments confirmed the powerful anti-inflammation induced by EVM. EVM also showed significant higher accumulation to inflammatory lungs compared with healthy ones, which was beneficial to the treatment of ALI/ARDS. EVM improved pulmonary function, attenuated lung injury, and reduced mortality in ALI mice with high levels of biocompatibility, exhibiting a 5-fold higher survival rate than the control. This type of artificial exosome emitted near-infrared light in the presence of laser activation, which endowed EVM with trackable ability both in vitro and in vivo. Our work developed a type of clinically used photosensitizer-loaded artificial exosome with membrane integrity and traceability. To the best of our knowledge, this kind of intracellularly synthesized artificial exosome was developed and showed great potential in ALI/ARDS therapy.
Keywords: acute lung injury; artificial exosomes; intracellular synthesis; mesenchymal stem cells; verteporfin.